For many years, researchers have known that putting worms, mice and other lab animals on low-calorie diets lengthens lifespan as much as 30 percent, but they haven't known why. Now a new study in C. elegans worms shows that the lengthening of lifespan depends on a biological process called autophagy, in which cells use their own proteins as nourishment. The research was published in the Sept. 5 issue of Science.

The investigators, led by Dr. Beth Levine, associate professor of medicine in P&S, found that when they turned off a key gene, bec-1, needed for autophagy, the worm's lifespan was shortened almost by half.

Other researchers have previously found that mutations in insulin signaling molecules also increase the lifespan of the worms by an unknown mechanism. Dr. Levine's research shows that the insulin signaling molecules inhibit the autophagy genes that are necessary for life extension. Humans have similar insulin signaling and autophagy genes suggesting similar processes may be at work in people. Defects in autophagy in people are also associated with tumor progression, heart disease, and some neurodegenerative disorders.

The paper also showed for the first time that autophagy plays a significant role in normal development. Without the bec-1 autophagy gene, the worm larva could not develop into the dauer stage, which allows the larva to survive harsh environmental conditions.

The research was supported by the NIH, American Cancer Society, and the Medical Research Council of the UK.